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The Impact of Genetic Variants for Different Physiological Characterization of Type 2 Diabetes Loci on Gestational Insulin Signaling in Nondiabetic Pregnant Chinese Women

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Abstract

We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m2) and gave them oral glucose tolerance tests. Matsuda index of insulin sensitivity, homeostatic model assessment of insulin resistance, indices of insulin disposition, early-phase insulin release, fasting state, and 0 to 120 minute’s proinsulin to insulin conversion were used to dissect insulin physiological characterization. Several variants related to β-cell function were genotyped. The genetic impacts were analyzed using logistic regression under an additive model. By adjusting for maternal age, BMI, and the related interactions, the genetic variants in ABCC8, CDKAL1, CDKN2A, HNF1B, KCNJ11, and MTNR1B were detected to impact gestational insulin signaling through heterogeneous mechanisms; however, compared with that in nonpregnant metabolism, the genetic effects seem to be eminently and heavily influenced by maternal age and BMI, indicating possible particular mechanisms underlying gestational metabolism and diabetic pathogenesis.

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Authors and Affiliations

  1. Diabetes Center & Institute of Transplantation, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Yihuanlu ** Deng MD

  2. Department of Medical Genetics, Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Yunqiang Liu PhD

  3. Columbia Center for Translational Immunology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    ** Deng MD

Authors
  1. Shunyao Liao PhD
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  2. Yunqiang Liu PhD
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  3. **aojuan Chen PhD
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  4. Yuande Tan PhD
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  5. Jie Mei MD
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  6. Wenzhong Song MD
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  7. Lu Gan PhD
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  12. Shao** Deng MD
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Correspondence to Shunyao Liao PhD or Shao** Deng MD.

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Liao, S., Liu, Y., Chen, X. et al. The Impact of Genetic Variants for Different Physiological Characterization of Type 2 Diabetes Loci on Gestational Insulin Signaling in Nondiabetic Pregnant Chinese Women. Reprod. Sci. 22, 1421–1428 (2015). https://doi.org/10.1177/1933719115580995

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